translation co-factor), MARCKS (myristylated alanine-rich C kinase substrate), Caponin (unknown function), and ERM (involved in linkage of the actin cytoskelton to the plasma membrane). Homologues The two mouse ROCK isoforms, ROCK1 and ROCK2, have high homology. They have 65% amino acid sequences in common and 92% homology within their kinase domains. ROCKs are homologous to other metazoan kinases such as myotonic dystrophy kinase (DMPK), DMPK-related cell division control protein 42 (Cdc42)-binding kinases (MRCK) and citron kinase. All of these kinases are composed of a N-terminal kinase domain, a coiled-coil structure and other functional motifs at the C-terminus Regulation ROCK is a downstream effector molecule of the Rho GTPase Rho that increases ROCK kinase activity when bound to it. Autoinhibition ROCK activity is regulated by the disruption of an intramolecular autoinhibition. In general, the structure of ROCK proteins consists of an N-terminal kinase domain, a coiled-coiled region and a PH domain containing a cystein-rich domain (CRD) at the C-terminal. A Rho-binding domain (RBD) is located in close proximity just in front of the PH domain. The kinase activity is inhibited by the intramolecular binding between the C-terminal cluster of RBD domain and the PH domain to the N-terminal kinase domain of ROCK. Thus, the kinase activity is off when ROCK is intramolecularly folded. The kinase activity is switched on when Rho-GTP binds to the Rho-binding domain of ROCK, disrupting the autoinhibitory interaction within ROCK, which liberates the kinase domain because ROCK is then no longer intramolecularly folded. Other regulators It has also been shown that Rho is not the only activator of ROCK. ROCK can also be regulated by lipids, in particular arachidonic acid, and protein oligomerization, which induces N-terminal transphosphorylation. Inhibitors Disease Research over the past two decades has shown that ROCK signaling plays an important role in many diseases including cardiovascular disease, neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, and cancer. For example, ROCK has been hypothesized to play an important role in the pleiotropic effects of statins. ROCK1/2 along with MRCKα/β kinases have been implicated in the plasticity of cancer cell migration, the phenomenon which bestows survival advantage to the cancer cells during drug treatments (drug resistance). Researchers are developing ROCK inhibitors such as RKI-1447 for treating various diseases including cancer. For example, such drugs have potential to prevent cancer from spreading by blocking cell migration, stopping cancer cells from spreading into neighboring